Prediction models for dementia and neuropathology in the oldest old: The Vantaa 85+ cohort study

Anette Hall, Timo Pekkala, Tuomo Polvikoski, Mark van Gils, Miia Kivipelto, Jyrki Lötjönen, Jussi Mattila, Mia Kero, Liisa Myllykangas, Mira Mäkelä, Minna Oinas, Anders Paetau, Hilkka Soininen, Maarit Tanskanen, Alina Solomon (Corresponding Author)

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    36 Citations (Scopus)


    Background: We developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort. Methods: We included participants without dementia at baseline and at least 2 years of follow-up (N = 245) for dementia prediction or with autopsy data (N = 163) for pathology. A supervised machine learning method was used for model development, considering sociodemographic, cognitive, clinical, vascular, and lifestyle factors, as well as APOE genotype. Neuropathological assessments included β-amyloid, neurofibrillary tangles and neuritic plaques, cerebral amyloid angiopathy (CAA), macro- and microscopic infarcts, α-synuclein pathology, hippocampal sclerosis, and TDP-43. Results: Prediction model performance was evaluated using AUC for 10 × 10-fold cross-validation. Overall AUCs were 0.73 for dementia, 0.64-0.68 for Alzheimer's disease (AD)- or amyloid-related pathologies, 0.72 for macroinfarcts, and 0.61 for microinfarcts. Predictors for dementia were different from those in previous reports of younger populations; for example, age, sex, and vascular and lifestyle factors were not predictive. Predictors for dementia versus pathology were also different, because cognition and education predicted dementia but not AD- or amyloid-related pathologies. APOE genotype was most consistently present across all models. APOE alleles had a different impact: ϵ4 did not predict dementia, but it did predict all AD- or amyloid-related pathologies; ϵ2 predicted dementia, but it was protective against amyloid and neuropathological AD; and ϵ3ϵ3 was protective against dementia, neurofibrillary tangles, and CAA. Very few other factors were predictive of pathology. Conclusions: Differences between predictors for dementia in younger old versus oldest old populations, as well as for dementia versus pathology, should be considered more carefully in future studies.

    Original languageEnglish
    Article number11
    JournalAlzheimer's Research and Therapy
    Publication statusPublished - 22 Jan 2019
    MoE publication typeA1 Journal article-refereed


    • Dementia
    • Neuropathology
    • Oldest old
    • Prediction
    • Supervised machine learning


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